Erythromycin and common derivatives are widely used and exhibit desirable activity against a number of gram-positive pathogens. Since some pathogens are less susceptible than others to these drugs, high doses of these antibiotics are occasionally necessary in the treatment of serious or widespread infections. As with all drugs, toxic effects are sometimes observed at higher dosage levels, particularly in patients who are seriously compromised by infection and thus are most in need of treatment. Unfortunately, improvements in potency and spectrum are often accompanied by an increase in toxicity, so that later generation drugs usually represent a compromise between these competing considerations. As a result, there is a continuing search for antibiotics which are more potent against certain organisms, or, preferably, against all organisms, than those currently used. Desirably, such drugs will have an improved therapeutic ratio, which is the ratio of the effective therapeutic or prophylactic dose to the toxic dose, usually expressed in terms of the ED.sub.50 /LD.sub.50 ratio.
It is an object of this invention to provide novel compounds which are derivatives of erythromycin, and which have greater in vitro and in vivo potency against certain organisms than erythromycin, reduced hepatotoxicity, and increased therapeutic ratios in comparison to erythromycin.
This and other objects of this invention will be more fully understood by reference to the following disclosure.
Biedrzycki, M., "Erythromycin Derivatives. Part VI. Carbamates of Cyclic 11,12-Carbonate of Erythromycin A", Polish Journal of Chemistry (Roczniki Chemii), 52, 315 (1978) describes the synthesis of the 4"-N-phenyl carbamate of erythromycin 11,12-cyclic carbonate.